Miranda Davies 1, 2, Alison Evans 1, 2, Flavien Coukan 1,2 , Lesley Wise1, Saad Shakir 1,2

Affiliations: 1 Drug Safety Research Unit, 2 University of Portsmouth

Background

Rivaroxaban is used to treat a range of conditions, including prevention of stroke and systemic embolism in patients with AF. This indication requires a fixed once-daily (od) dose (20mg) with dosage reduction to 15 mg once daily only recommended in patients (pts) with renal impairment (creatinine clearance 15-49 ml/min). However other clinical factors might be considered by the prescriber when choosing an initial dose.

Objectives

To describe the clinical characteristics of pts prescribed an initial dose of (≥ 20mg and <20 mg daily) for treatment of AF in secondary care.

Methods

The ROSE study was a specialist cohort event monitoring study of pts prescribed rivaroxaban. Specialists provided information from medical records via questionnaires at baseline and ≥ 12 weeks. Information on the prescribed initial dose and baseline characteristics including risk factors for bleeding (HAS-BLED criteria) was collected. For pts prescribed a reduced initial dose (<20 mg daily), we assessed clinical characteristics vs. pts prescribed ≥ 20mg daily.

Results

The cohort consisted of 965 pts with AF; of whom (18.3%, n=177), were prescribed an initial dose of <20 mg daily (15mg od [n=173]; 10mg od [n=3]; 4mg od [n=1]). The majority were female (57.6%, median age 84 yrs) vs. pts prescribed ≥ 20mg daily (20mg od [n=750]; 30mg od [n=16]), where the majority were male (56.4%, median age 75 yrs). 36/177 (20.3%) pts had a history of CKD 3-4 or 5. For 22 patients the start dose was unknown. Frequency of HAS-BLED criteria in pts prescribed <20 mg daily vs. ≥ 20mg daily was: Hypertension (37.3% vs. 38.5%), Abnormal renal function (Chronic dialysis, renal transplant, serum creatinine ≥ 2.3 mg/dL or 200 µmol/L) (3.4% vs. 1.2%), Abnormal liver function (0.6% vs. 1.0%), History of Stroke (31.1% vs. 30.4%), History of Bleeding/predisposition (18.6% vs. 16.3%), Labile INR (N/A), Age ≥65 yrs (96.1% vs. 81.2%), Drug therapy (52.0% vs. 51.4%), Alcohol (0% vs. 4.8%).

Conclusion

In pts prescribed a reduced total daily dose of rivaroxaban <20 mg od, there were a higher proportion of females and those aged ≥65 yrs. Patients prescribed this lower dose were also more likely to have abnormal renal function, defined as per HAS-BLED, than those patients prescribed ≥ 20mg daily. Although the label recommends dose reduction in AF pts with renal impairment, other factors seem to impact the choice of the initial dose in the clinical setting.